Dusts generated during demolition of buildings, remediation, and construction may be contaminated with toxic particulates including metals and asbestos fibers. Three forms of asbestos are on the CERCLA Priority List of Hazardous Substances and it is a common contaminant at former industrial sites and military bases. However, the potential adverse health effects resulting from inhalation of mixed dusts from these asbestos-contaminated sites are unknown. The availability of transition metals, especially iron, to participate in redox cycling leading to generation of free radicals has been hypothesized to play an important role in asbestos-induced lung diseases. It is hypothesized that contamination with iron and asbestos fibers will potentiate the toxicity of mixed dust exposures due to enhanced iron mobilization, redox cycling, and generation of reactive oxygen species. The ultimate goal of this project is to develop a panel of cellular and molecular endpoints that can be integrated into a short-term screening strategy to identify toxic mixed dusts. The Specific Aims to achieve this goal are: a) To generate and characterize model dust samples composed of inert particles, metal-contaminated particles, and asbestos fibers; b) To assess mobilization of transition metals and redox activity of these model dust samples in vitro; c) To develop a gene expression profile that will differentiate between nontoxic and toxic dusts; d) To explore the mechanisms of mixed dust-fiber toxicity using short-term in vitro assays; and e) To validate this testing strategy in a chronic carcinogenicity assay.